Animal models of major depressive disorder and the implications for drug discovery and development

Konstantin A. Demin, Maxim Sysoev, Maria V. Chernysh, Anna K. Savva, Mamiko Koshiba, Edina A. Wappler-Guzzetta, Cai Song, Murilo S. De Abreu, Brian Leonard, Matthew O. Parker, Brian H. Harvey, Li Tian, Eero Vasar, Tatyana Strekalova, Tamara G. Amstislavskaya, Andrey D. Volgin, Erik T. Alpyshov, Dongmei Wang, Allan V. Kalueff

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)

Abstract

Introduction: Depression is a highly debilitating psychiatric disorder that affects the global population and causes severe disabilities and suicide. Depression pathogenesis remains poorly understood, and the disorder is often treatment-resistant and recurrent, necessitating the development of novel therapies, models and concepts in this field. Areas covered: Animal models are indispensable for translational biological psychiatry, and markedly advance the study of depression. Novel approaches continuously emerge that may help untangle the disorder heterogeneity and unclear categories of disease classification systems. Some of these approaches include widening the spectrum of model species used for translational research, using a broader range of test paradigms, exploring new pathogenic pathways and biomarkers, and focusing more closely on processes beyond neural cells (e.g. glial, inflammatory and metabolic deficits). Expert opinion: Dividing the core symptoms into easily translatable, evolutionarily conserved phenotypes is an effective way to reevaluate current depression modeling. Conceptually novel approaches based on the endophenotype paradigm, cross-species trait genetics and ‘domain interplay concept’, as well as using a wider spectrum of model organisms and target systems will enhance experimental modeling of depression and antidepressant drug discovery.

Original languageEnglish
Pages (from-to)365-378
Number of pages14
JournalExpert Opinion on Drug Discovery
Volume14
Issue number4
DOIs
Publication statusPublished - 2019 Apr 3
Externally publishedYes

Keywords

  • Depression
  • animal modeling
  • endophenotype
  • major depressive disorder
  • pathogenesis

ASJC Scopus subject areas

  • Drug Discovery

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